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1.  Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer 
Background
A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer.
Methods
A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation.
Results
The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities.
Conclusions
EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.
doi:10.1186/1748-717X-5-67
PMCID: PMC2914666  PMID: 20646289
2.  Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study 
OncoTargets and therapy  2010;3:197-203.
Background:
This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer.
Methods:
Medical records were reviewed from 41 patients (age 40–89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina.
Results:
Median follow-up was 3.8 (range 0.5–12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date.
Conclusion:
Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate.
PMCID: PMC2962306  PMID: 21049086
endometrial cancer; electronic brachytherapy; radiation therapy
3.  Surgical perspectives from a prospective, nonrandomized, multicenter study of breast conserving surgery and adjuvant electronic brachytherapy for the treatment of breast cancer 
Background
Accelerated partial breast irradiation (APBI) may be used to deliver radiation to the tumor bed post-lumpectomy in eligible patients with breast cancer. Patient and tumor characteristics as well as the lumpectomy technique can influence patient eligibility for APBI. This report describes a lumpectomy procedure and examines patient, tumor, and surgical characteristics from a prospective, multicenter study of electronic brachytherapy.
Methods
The study enrolled 65 patients of age 45-84 years with ductal carcinoma or ductal carcinoma in situ, and 44 patients, who met the inclusion and exclusion criteria, were treated with APBI using the Axxent® electronic brachytherapy system following lumpectomy. The prescription dose was 34 Gy in 10 fractions over 5 days.
Results
The lumpectomy technique as described herein varied by site and patient characteristics. The balloon applicator was implanted by the surgeon (91%) or a radiation oncologist (9%) during or up to 61 days post-lumpectomy (mean 22 days). A lateral approach was most commonly used (59%) for insertion of the applicator followed by an incision site approach in 27% of cases, a medial approach in 5%, and an inferior approach in 7%. A trocar was used during applicator insertion in 27% of cases. Local anesthetic, sedation, both or neither were administered in 45%, 2%, 41% and 11% of cases, respectively, during applicator placement. The prescription dose was delivered in 42 of 44 treated patients.
Conclusions
Early stage breast cancer can be treated with breast conserving surgery and APBI using electronic brachytherapy. Treatment was well tolerated, and these early outcomes were similar to the early outcomes with iridium-based balloon brachytherapy.
doi:10.1186/1477-7819-9-30
PMCID: PMC3065420  PMID: 21385371
4.  The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer 
Background
Millions of people are diagnosed with non-melanoma skin cancers (NMSC) worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope.
Methods
Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed.
Results
Thirty-seven patients (mean age 72.5 years) with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89%) were T1, 1 (2%) Tis, 1 (2%) T2, and 3 (7%) lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%), ear 5 (11%), scalp 5 (11%), face 14 (32%), and an extremity for 4 (9%). Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up.
Conclusions
The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.
doi:10.1186/1748-717X-5-87
PMCID: PMC2957390  PMID: 20875139
5.  Post-surgical treatment of early-stage breast cancer with electronic brachytherapy: an intersociety, multicenter brachytherapy trial 
OncoTargets and therapy  2010;3:211-218.
Introduction
Electronic brachytherapy (EBT) was developed to allow accelerated partial breast irradiation to be performed in a patient procedure room with minimal shielding. This observational, nonrandomized, multicenter study evaluated EBT as a post-surgical adjuvant radiation therapy for early stage breast cancer.
Methods
This study included women aged 50 years or more with invasive carcinoma or ductal carcinoma in situ, tumor size ≤3 cm, negative lymph node status, and negative surgical margins. The endpoints were skin and subcutaneous toxicities, efficacy outcomes, cosmetic outcomes, and device performance. In this interim report, 1-month, 6-month, and 1-year follow-up data are available on 68, 59, and 37 patients, respectively.
Results
The EBT device performed consistently, delivering the prescribed 34 Gy to all 69 patients (10 fractions/patient). Most adverse events were Grade 1 and included firmness, erythema, breast tenderness, hyperpigmentation, pruritis, field contracture, seroma, rash/desquamation, palpable mass, breast edema, hypopigmentation, telangiectasia, and blistering, which were anticipated. Breast infection occurred in two (2.9%) patients. No tumor recurrences were reported. Cosmetic outcomes were excellent or good in 83.9%–100% of evaluable patients at 1 month, 6 months, and 1 year.
Conclusion
This observational, nonrandomized, multicenter study demonstrates that this EBT device was reliable and well tolerated as an adjuvant radiation therapy for early stage breast cancer.
doi:10.2147/OTT.S14514
PMCID: PMC2994203  PMID: 21124748
radiation therapy; electronic brachytherapy; breast cancer
6.  Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer 
Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT). Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P < 0.001). There was a trend towards higher rate of pathologic CR for EBT (P = 0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P = 0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.
doi:10.1155/2012/406568
PMCID: PMC3399366  PMID: 22830003
7.  Evaluation of Gafchromic EBT2 film for the measurement of anisotropy function for high-dose-rate 192Ir brachytherapy source with respect to thermoluminescent dosimetry 
Aim
The aim of this work was to assess the suitability of the use of a Gafchromic EBT2 film for the measurement of anisotropy function for microSelectron HDR 192Ir (classic) source with a comparative dosimetry method using a Gafchromic EBT2 film and thermoluminescence dosimeters (TLDs).
Background
Sealed linear radiation sources are commonly used for high dose rate (HDR) brachytherapy treatments. Due to self-absorption and oblique filtration of radiation in the source capsule material, an inherent anisotropy is present in the dose distribution around the source which can be described by a measurable two-dimensional anisotropy function, F(r, θ).
Materials and methods
Measurements were carried out in a specially designed and locally fabricated PMMA phantom with provisions to accommodate miniature LiF TLD rods and EBT2 film dosimeters at identical radial distances with respect to the 192Ir source.
Results
The data of anisotropy function generated by the use of the Gafchromic EBT2 film method are in agreement with their TLD measured values within 4%. The produced data are also consistent with their experimental and Monte Carlo calculated results for this source available in the literature.
Conclusion
Gafchromic EBT2 film was found to be a feasible dosimeter in determining anisotropy in the dose distribution of 192Ir source. It offers high resolution and is a viable alternative to TLD dosimetry at discrete points. The method described in this paper is useful for comparing the performances of detectors and can be applied for other brachytherapy sources as well.
doi:10.1016/j.rpor.2010.11.003
PMCID: PMC3863320  PMID: 24376951
Anisotropy function; TL dosimetry; Gafchromic EBT2 film; HDR 192Ir source
8.  Dosimetry evaluation of SAVI-based HDR brachytherapy for partial breast irradiation 
Accelerated partial breast irradiation (APBI) with high dose rate (HDR) brachytherapy offers an excellent compact course of radiation due to its limited number of fractions for early-stage carcinoma of breast. One of the recent devices is SAVI (strut-adjusted volume implant), which has 6, 8 or 10 peripheral source channels with one center channel. Each channel can be differentially loaded. This paper focuses on the treatment planning, dosimetry and quality assurance aspects of HDR brachytherapy implant with GammaMed Plus HDR afterloader unit. The accelerated PBI balloon devices normally inflate above 35 cc range, and hence these balloon type devices cannot be accommodated in small lumpectomy cavity sizes. CT images were obtained and 3-D dosimetric plans were done with Brachyvision planning system. The 3-D treatment planning and dosimetric data were evaluated with planning target volume (PTV)_eval V90, V95, V150, V200 skin dose and minimum distance to skin. With the use of the SAVI 6-1 mini device, we were able to accomplish an excellent coverage — V90, V95, V150 and V200 to 98%, 95%, 37 cc (<50 cc volume) and 16 cc (<20 cc volume), respectively. Maximum skin dose was between 73% and 90%, much below the prescribed dose of 34 Gy. The minimum skin distance achieved was 5 to 11 mm. The volume that received 50% of the prescribed radiation dose was found to be lower with SAVI. The multi-channel SAVI-based implants reduced the maximum skin dose to markedly lower levels as compared to other modalities, simultaneously achieving best dose coverage to target volume. Differential-source dwell-loading allows modulation of the radiation dose distribution in symmetric or asymmetric opening of the catheter shapes and is also advantageous in cavities close to chest wall.
doi:10.4103/0971-6203.62127
PMCID: PMC2936181  PMID: 20927219
Accelerated partial breast irradiation; high dose rate; SAVI
9.  Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer 
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
doi:10.4103/0971-6203.62201
PMCID: PMC2884303  PMID: 20589121
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
10.  The dosimetric impact of vaginal balloon-packing on intracavitary high-dose-rate brachytherapy for gynecological cancer 
Purpose
We perform a clinical retrospective study to determine whether a vaginal balloon-packing system provides a dosimetric reduction to organs at risk (OARs) versus traditional gauze packing for gynecological high-dose-rate brachytherapy (HDR-BT). We also test various balloon filling materials for optimizing imaging quality.
Material and methods
Filling materials for balloon-packing were evaluated based on imaging quality with X-ray, computerized tomography, and magnetic resonance imaging modalities. We then retrospectively reviewed 45 HDR-BT plans of 18 patients performed with gauze packing and 39 plans of 16 patients performed with balloon-packing. Twelve patients received both gauze and balloon-packing. HDR-BT was delivered with an iridium-192 afterloader and a Fletcher-Suit-Declos-style T&O applicator. At each fraction, 3D imaging was obtained. The D2cc values of OARs were calculated, as well as ICRU-defined point doses.
Results
In the 84 HDR fractions reviewed, vaginal balloon-packing provides statistically equivalent doses to rectum, bladder, and sigmoid compared to gauze packing. On average balloon-packing produced average reductions of 3.3% and 6.9% in the rectal and sigmoid D2cc doses and an increase of 3.2% to the bladder D2cc dose (normalized to prescription dose), although none of these values were statistically significant for the twelve patients who received both gauze and balloon-packing (32 and 40 total fractions, respectively).
Conclusions
In the 84 HDR fractions analyzed, vaginal balloon-packing is as effective as gauze packing for dose sparing to the rectum, bladder, and sigmoid. A 1: 1 solution of saline and contrast for filling material enables easy contouring for image-guided HDR with minimal artefacts.
doi:10.5114/jcb.2013.34449
PMCID: PMC3635049  PMID: 23634151
brachytherapy; gynecological cancer; high-dose-rate brachytherapy; vaginal balloon packing
11.  Doses to internal organs for various breast radiation techniques - implications on the risk of secondary cancers and cardiomyopathy 
Background
Breast cancers are more frequently diagnosed at an early stage and currently have improved long term outcomes. Late normal tissue complications induced by adjuvant radiotherapy like secondary cancers or cardiomyopathy must now be avoided at all cost. Several new breast radiotherapy techniques have been developed and this work aims at comparing the scatter doses of internal organs for those techniques.
Methods
A CT-scan of a typical early stage left breast cancer patient was used to describe a realistic anthropomorphic phantom in the MCNP Monte Carlo code. Dose tally detectors were placed in breasts, the heart, the ipsilateral lung, and the spleen. Five irradiation techniques were simulated: whole breast radiotherapy 50 Gy in 25 fractions using physical wedge or breast IMRT, 3D-CRT partial breast radiotherapy 38.5 Gy in 10 fractions, HDR brachytherapy delivering 34 Gy in 10 treatments, or Permanent Breast 103Pd Seed Implant delivering 90 Gy.
Results
For external beam radiotherapy the wedge compensation technique yielded the largest doses to internal organs like the spleen or the heart, respectively 2,300 mSv and 2.7 Gy. Smaller scatter dose are induced using breast IMRT, respectively 810 mSv and 1.1 Gy, or 3D-CRT partial breast irradiation, respectively 130 mSv and 0.7 Gy. Dose to the lung is also smaller for IMRT and 3D-CRT compared to the wedge technique. For multicatheter HDR brachytherapy a large dose is delivered to the heart, 3.6 Gy, the spleen receives 1,171 mSv and the lung receives 2,471 mSv. These values are 44% higher in case of a balloon catheter. In contrast, breast seeds implant is associated with low dose to most internal organs.
Conclusions
The present data support the use of breast IMRT or virtual wedge technique instead of physical wedges for whole breast radiotherapy. Regarding partial breast irradiation techniques, low energy source brachytherapy and external beam 3D-CRT appear safer than 192Ir HDR techniques.
doi:10.1186/1748-717X-6-5
PMCID: PMC3027128  PMID: 21235766
12.  Thermal boost combined with interstitial brachytherapy in breast conserving therapy – Assessment of early toxicity 
Background
Hyperthermia (HT) causes a direct damage to cancerous cells and/or sensitize them to radiotherapy with usually minimal injury to normal tissues. Adjuvant HT is probably one of the most effective radiation sensitizers known and works best when delivered simultaneously with radiation. In breast conserving therapy, irradiation has to minimize the risk of local relapse within the treated breast, especially in an area of a tumor bed. Brachytherapy boost reduces 5-year local recurrence rate to mean 5,5%, so there still some place for further improvement. The investigated therapeutic option is an adjuvant single session of local HT (thermal boost) preceding standard CT-based multicatheter interstitial HDR brachytherapy boost in order to increase the probability of local cure.
Aim
To report the short-term results in regard to early toxicity of high-dose-rate (HDR) brachytherapy (BT) boost with or without interstitial microwave hyperthermia (MV HT) for early breast cancer patients treated with breast conserving therapy (BCT).
Materials and methods
Between February 2006 and December 2007, 57 stage IA–IIIA breast cancer patients received a 10 Gy HDR BT boost after conservative surgery and 42.5–50 Gy whole breast irradiation (WBI) ± adjuvant chemotherapy. 32 patients (56.1%) were treated with additional pre-BT single session of interstitial MW HT to a tumor bed (multi-catheter technique). Reference temperature was 43 °C and therapeutic time (TT) was 1 h. Incidence, severity and duration of radiodermatitis, skin oedema and skin erythema in groups with (I) or without HT (II) were assessed, significant p-value ≤ 0.05.
Results
Median follow-up was 40 months. Local control was 100% and distant metastasis free survival was 91.1%. HT sessions (median): reference temperature 42.2 °C, therapeutic time (TT) 61.4 min, total thermal dose 42 min and a gap between HT and BT 30 min. Radiodermatitis grades I and II occurred in 24 and 6 patients, respectively, differences between groups I and II were not significant. Skin oedema and erythema occurred in 48 (85.7%) and 36 (64.3%) cases, respectively, and were equally distributed between the groups. The incidence and duration of skin oedema differed between the subgroups treated with different fractionation protocols of WBI, p = 0.006. Skin oedema was present up to 12 months. No difference in pattern of oedema regression between groups I and II was observed, p = 0.933.
Conclusion
Additional thermal boost preceding standard HDR BT boost has a potential of further improvement in breast cancer local control in BCT. Pre-BT hyperthermia did not increase early toxicity in patients treated with BCT and was well tolerated. All side effects of combined treatment were transient and were present for up to 12 months. The increase in incidence of skin oedema was related to hypofractionated protocols of WBI. The study has to be randomized and continued on a larger group of breast cancer patients to verify the potential of local control improvement and to assess the profile of late toxicity.
doi:10.1016/j.rpor.2011.02.004
PMCID: PMC3863141  PMID: 24376963
Hyperthermia; Brachytherapy boost; Breast cancer
13.  Accelerated Partial Breast Irradiation (APBI): A review of available techniques 
Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.
doi:10.1186/1748-717X-5-90
PMCID: PMC2958971  PMID: 20920346
14.  Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study 
BMC Cancer  2005;5:79.
Background
Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures.
Methods
Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation.
Results
With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range.
Conclusion
In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.
doi:10.1186/1471-2407-5-79
PMCID: PMC1181808  PMID: 16026629
15.  Monte Carlo simulations and radiation dosimetry measurements of peripherally applied HDR 192Ir breast brachytherapy D-shaped applicators 
Medical physics  2009;36(3):809-815.
Conformal dose coverage for accelerated partial breast irradiation or radiotherapy boost can be obtained with AccuBoost® D-shaped brachytherapy applicators using a flattened surface positioned near the patient. Three D-shaped applicators (D45/D53/D60) were dosimetrically characterized using Monte Carlo methods (MCNP5), air ionization chambers (Farmer and Markus), and radiochromic film (GafChromic EBT) in polystyrene and ICRU 44 breast tissue. HDR 192Ir source dwell times were either constant or optimized to improve skin dose uniformity. Scatter dose decreased as depth decreased. 10 mm beyond the applicator aperture, dose reductions of 90% and 51% were observed at depths of 0 and 30 mm, respectively. Similarly, planar dose uniformity improved as depth decreased and was also due to scatter and applicator geometry. Dose uniformity inside the applicator aperture was approximately 11% and 15% for all three applicators at the skin and 30 mm deep, respectively. Depth dose measurements in polystyrene using ion chamber and radiochromic film agreed with Monte Carlo results within 2%. Discrepancies between film and Monte Carlo dose profiles at 30 mm depth were within 1%.
doi:10.1118/1.3075818
PMCID: PMC2674240  PMID: 19378741
16.  High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up 
Journal of Radiation Research  2013;55(3):509-517.
The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.
doi:10.1093/jrr/rrt128
PMCID: PMC4014151  PMID: 24222312
high-dose-rate brachytherapy; prostate cancer; androgen deprivation therapy; high-risk; very high-risk
17.  Dose correction in lung for HDR breast brachytherapy 
Purpose
To evaluate the dosimetric impact of lung tissue in Ir-192 APBI.
Material and methods
In a 40 × 40 × 40 cm3 water tank, an Accelerated Partial Breast Irradiation (APBI) brachytherapy balloon inflated to 4 cm diameter was situated directly below the center of a 30 × 30 × 1 cm3 solid water slab. Nine cm of solid water was stacked above the 1 cm base. A parallel plate ion chamber was centered above the base and ionization current measurements were taken from the central HDR source dwell position for channels 1, 2, 3 and 5 of the balloon. Additional ionization data was acquired in the 9 cm stack at 1 cm increments. A comparable data set was also measured after replacing the 9 cm solid water stack with cork slabs. The ratios of measurements in the two phantoms were calculated and compared to predicted results of a commercial treatment planning system.
Results
Lower dose was measured in the cork within 1 cm of the cork/solid water interface possibly due to backscatter effects. Higher dose was measured beyond 1 cm from the cork/solid water interface, increasing with path length up to 15% at 9 cm depth in cork. The treatment planning system did not predict either dose effect.
Conclusions
This study investigates the dosimetry of low density material when the breast is treated with Ir-192 brachytherapy. HDR dose from Ir-192 in a cork media is shown to be significantly different than in unit density media. These dose differences are not predicted in most commercial brachytherapy planning systems. Empirical models based on measurements could be used to estimate lung dose associated with HDR breast brachytherapy.
doi:10.5114/jcb.2012.29367
PMCID: PMC3552632  PMID: 23349652
lung; dosimetry; partial breast irradiation; HDR
18.  A study on rectal dose measurement in phantom and in vivo using Gafchromic EBT3 film in IMRT and CyberKnife treatments of carcinoma of prostate 
The objective of this study is to check the feasibility of in vivo rectal dose measurement in intensity-modulated radiotherapy (IMRT) and CyberKnife treatments for carcinoma prostate. An in-house pelvis phantom made with bee's wax was used in this study. Two cylindrical bone equivalent materials were used to simulate the femur. Target and other critical structures associated with carcinoma prostate were delineated on the treatment planning images by the radiation oncologist. IMRT treatment plan was generated in Oncentra Master Plan treatment planning system and CyberKnife treatment plan was generated in Multiplan treatment planning system. Dose measurements were carried out in phantom and in patient using Gafchromic EBT3 films. RIT software was used to analyze the dose measured by EBT3 films. The measured doses using EBT3 films were compared with the TPS-calculated dose along the anterior rectal wall at multiple points. From the in-phantom measurements, it is observed that the difference between calculated and measured dose was mostly within 5%, except for a few measurement points. The difference between calculated and measured dose in the in-patient measurements was higher than 5% in regions which were away from the target. Gafchromic EBT3 film is a suitable detector for in vivo rectal dose measurements as it offers the possibility of analyzing the dose at multiple points. In addition, the method of extending this in vivo rectal dose measurement technique as a tool for patient-specific quality assurance check is also analyzed.
doi:10.4103/0971-6203.116372
PMCID: PMC3775037  PMID: 24049320
Gafchromic EBT3; in vivo dosimetry; rectal dose measurement
19.  A Phase II Trial of Brachytherapy Alone Following Lumpectomy for Select Breast Cancer: tumor control and survival outcomes of RTOG 95-17 
Purpose:
RTOG 95-17 is a prospective Phase II cooperative group trial of APBI alone using multicatheter brachytherapy following lumpectomy in select early stage breast cancers. Tumor control and survival outcomes are reported.
Materials and Methods:
Eligibility criteria included stage I/II breast carcinoma confirmed to be <3cm, unifocal, invasive non-lobular histology with 0-3 positive axillary nodes without extracapsular extension. APBI treatment was delivered with either Low Dose Rate (LDR) (45 Gy in 3.5-5 days) or High Dose Rate (HDR) (34 Gy in 10 BID fractions over 5 days). Endpoints evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison.
Results:
Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR and 33 treated with LDR. Eighty seven patients had T1 lesions and 12 had T2 lesions. Seventy nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional and contralateral failure rates of 3%, 5% and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional and contralateral failure rates of 6%, 0% and 6%, respectively.
Conclusion:
Patients treated with multicatheter partial breast brachytherapy on this trial experienced excellent in-breast control rates and overall outcome that compare to reports from APBI studies with similar extended follow-up.
doi:10.1016/j.ijrobp.2007.12.056
PMCID: PMC2604132  PMID: 18294778
Brachytherapy; breast cancer; breast cancer trials; radiation therapy for breast cancer; accelerated partial breast irradiation
20.  Association Between Treatment With Brachytherapy vs Whole-Breast Irradiation and Subsequent Mastectomy, Complications, and Survival Among Older Women With Invasive Breast Cancer 
Jama  2012;307(17):1827-1837.
Context
Brachytherapy is a radiation treatment that uses an implanted radioactive source. In recent years, use of breast brachytherapy after lumpectomy for early breast cancer has increased substantially despite a lack of randomized trial data comparing its effectiveness with standard whole-breast irradiation (WBI). Because results of long-term randomized trials will not be reported for years, detailed analysis of clinical outcomes in a nonrandomized setting is warranted.
Objective
To compare the likelihood of breast preservation, complications, and survival for brachytherapy vs WBI among a nationwide cohort of older women with breast cancer with fee-for-service Medicare.
Design
Retrospective population-based cohort study of 92 735 women aged 67 years or older with incident invasive breast cancer, diagnosed between 2003 and 2007 and followed up through 2008. After lumpectomy 6952 patients were treated with brachytherapy vs 85 783 with WBI.
Main Outcome Measures
Cumulative incidence and adjusted risk of subsequent mastectomy (an indicator of failure to preserve the breast) and death were compared using the log-rank test and proportional hazards models. Odds of postoperative infectious and noninfectious complications within 1 year were compared using the χ2 test and logistic models. Cumulative incidences of long-term complications were compared using the log-rank test.
Results
Five-year incidence of subsequent mastectomy was higher in women treated with brachytherapy (3.95%; 95% CI, 3.19%–4.88%) vs WBI (2.18%; 95% CI, 2.04%–2.33%; P<.001) and persisted after multivariate adjustment (hazard ratio [HR], 2.19; 95% CI, 1.84–2.61, P<.001). Brachytherapy was associated with more frequentinfectious (16.20%; 95% CI, 15.34%–17.08% vs 10.33%; 95% CI, 10.13%–10.53%; P<.001; adjusted odds ratio [OR], 1.76; 1.64–1.88) and noninfectious (16.25%; 95% CI, 15.39%–17.14% vs 9.00%; 95% CI, 8.81%–9.19%; P<.001; adjusted OR, 2.03; 95% CI, 1.89–2.17) postoperative complications; and higher 5-year incidence of breast pain (14.55%, 95% CI, 13.39%–15.80% vs 11.92%; 95% CI, 11.63%–12.21%), fat necrosis (8.26%; 95% CI, 7.27–9.38 vs 4.05%; 95% CI, 3.87%–4.24%), and rib fracture (4.53%; 95% CI, 3.63%–5.64% vs 3.62%; 95% CI, 3.44%–3.82%; P≤.01 for all). Five-year overall survival was 87.66% (95% CI, 85.94%–89.18%) in patients treated with brachytherapy vs 87.04% (95% CI, 86.69%–87.39%) in patients treated with WBI (adjusted HR, 0.94; 95% CI, 0.84–1.05; P=.26).
Conclusion
In a cohort of older women with breast cancer, treatment with brachytherapy compared with WBI was associated with worse long-term breast preservation and increased complications but no difference in survival.
doi:10.1001/jama.2012.3481
PMCID: PMC3397792  PMID: 22550197
21.  Brachytherapy in the therapy of prostate cancer – an interesting choice 
Contemporary Oncology  2013;17(5):407-412.
Brachytherapy is a curative alternative to radical prostatectomy or external beam radiation [i.e. 3D conformal external beam radiation therapy (CRT), intensity-modulated radiation therapy (IMRT)] with comparable long-term survival and biochemical control and the most favorable toxicity. HDR brachytherapy (HDR-BT) in treatment of prostate cancer is most frequently used together with external beam radiation therapy (EBRT) as a boost (increasing the treatment dose precisely to the tumor). In the early stages of the disease (low, sometimes intermediate risk group), HDR-BT is more often used as monotherapy. There are no significant differences in treatment results (overall survival rate – OS, local recurrence rate – LC) between radical prostatectomy, EBRT and HDR-BT. Low-dose-rate brachytherapy (LDR-BT) is a radiation method that has been known for several years in treatment of localized prostate cancer. The LDR-BT is applied as a monotherapy and also used along with EBRT as a boost. It is used as a sole radical treatment modality, but not as a palliative treatment. The use of brachytherapy as monotherapy in treatment of prostate cancer enables many patients to keep their sexual functions in order and causes a lower rate of urinary incontinence. Due to progress in medical and technical knowledge in brachytherapy (“real-time” computer planning systems, new radioisotopes and remote afterloading systems), it has been possible to make treatment time significantly shorter in comparison with other methods. This also enables better protection of healthy organs in the pelvis. The aim of this publication is to describe both brachytherapy methods.
doi:10.5114/wo.2013.38557
PMCID: PMC3934024  PMID: 24596528
HDR brachytherapy; LDR brachytherapy; prostate cancer; seeds
22.  Radiation therapy for primary vaginal carcinoma 
Journal of Radiation Research  2013;54(5):931-937.
Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2–T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2–T3 disease resulted in good local control.
doi:10.1093/jrr/rrt028
PMCID: PMC3766300  PMID: 23559599
primary vaginal cancer; radiation therapy; high-dose-rate brachytherapy; intracavitary brachytherapy; interstitial brachytherapy
23.  High dose rate brachytherapy for oral cancer 
Journal of Radiation Research  2012;54(1):1-17.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
doi:10.1093/jrr/rrs103
PMCID: PMC3534285  PMID: 23179377
brachytherapy; oral cancer; high dose rate
24.  Application of a color scanner for 60Co high dose rate brachytherapy dosimetry with EBT radiochromic film 
Radiology and Oncology  2012;46(4):363-369.
Background.
The aim of this study is to evaluate the performance of a color scanner as a radiochromic film reader in two dimensional dosimetry around a high dose rate brachytherapy source.
Materials and methods
A Microtek ScanMaker 1000XL film scanner was utilized for the measurement of dose distribution around a high dose rate GZP6 60Co brachytherapy source with GafChromic® EBT radiochromic films. In these investigations, the non-uniformity of the film and scanner response, combined, as well as the films sensitivity to scanner’s light source was evaluated using multiple samples of films, prior to the source dosimetry. The results of these measurements were compared with the Monte Carlo simulated data using MCNPX code. In addition, isodose curves acquired by radiochromic films and Monte Carlo simulation were compared with those provided by the GZP6 treatment planning system.
Results
Scanning of samples of uniformly irradiated films demonstrated approximately 2.85% and 4.97% nonuniformity of the response, respectively in the longitudinal and transverse directions of the film. Our findings have also indicated that the film response is not affected by the exposure to the scanner’s light source, particularly in multiple scanning of film. The results of radiochromic film measurements are in good agreement with the Monte Carlo calculations (4%) and the corresponding dose values presented by the GZP6 treatment planning system (5%).
Conclusions
The results of these investigations indicate that the Microtek ScanMaker 1000XL color scanner in conjunction with GafChromic EBT film is a reliable system for dosimetric evaluation of a high dose rate brachytherapy source.
doi:10.2478/v10019-012-0015-1
PMCID: PMC3572889  PMID: 23411947
color scanner; GZP6 brachytherapy source; 60Co high dose rate source; HDR; EBT radiochromic film
25.  High Dose Rate Brachytherapy in the Treatment of cervical cancer: preliminary experience with cobalt 60 Radionuclide source—A Prospective Study 
Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings.
Objective:
To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer.
Methods:
Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0.
Results:
The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results.
Conclusion:
Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
PMCID: PMC2934612  PMID: 20838638
HDR brachytherapy; Co-60 source; cervical cancer; acute toxicity

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